Mitomycin C is the principal mitomycin produced by fermentation and is the commercially available form.
A useful semisynthetic approach to forming 7-substituted amino-9a-methoxymitosanes has centered on converting mitomycin C to the final product via mitomycin A as an intermediate where mitomycin C is converted to mitomycin A by hydrolyzing to form the corresponding 7-hydroxymitosane and methylating that compound with diazomethane as described, for example, in Vyas et al U.S. Pat. No. 4,691,023 or with 3-methyl-1-p-tolyltriazene as described, for example in Vyas, D. M., et al, J. Org. Chem. 1986, 51, 4307-4309. The procedure utilizing diazomethane has the disadvantage that this reactant is very hazardous to handle and therefore undesirable for routine and large scale synthesis. The triazene route has the disadvantages of producing by-product toluidine which can react with mitomycin A product and which requires removal and of requiring the absence of water since the triazene reactant is unstable in the presence of water.
It is an object herein to provide a novel compound which is an intermediate for production of 7-substituted amino, 7-amino and 7-substituted oxy-9a-methoxymitosanes which is synthesized utilizing a much safer reactant than diazomethane and without the formation of by-product and which is readily prepared in the presence of water, and which also is useful as an antitumor agent.
It is a further object herein to provide methods of making such compound.
It is a further object herein to provide a method of converting said compound to 7-[2-(4nitrophenylditho)ethyl-amino]-9a-methoxymitosane.